Extensions of previous work and new projects are proposed in the following areas: 1) Studies on the isolation and in vitro translation of proinsulin messenger RNA and the characterization of preproinsulin, the in vitro translation product of this messenger RNA; 2) Continued studied on insulins and proinsulins from various species and on the subcellular organization of the insulin biosynthetic machinery of the beta cell; 3) Isolation and characterization of beta cell plasma membranes; 4) Studies on insulin binding, degradation and biological action in the liver, and the relationship of these actions to insulin structure; 5) Tissue culture studies with normal islets and induced beta cell tumors in rats and mice; 6) Studies on glucagon precursors are being conducted largely by Dr. H.S. Tager and his colleagues. BIBLIOGRAPHIC REFERENCES: Terris, S., and Steiner, D.F. Retention and degradation of 125I-insulin by perfused rat livers. J. Clin. Invest., 57, 885-896 (1976). Chan, S.J., Keim, P., and Steiner, D.F. Cell-free synthesis of rat preproinsulins: Characterization and partial amino acid sequence determination. Proc. Natl. Acad. Sci., U.S.A., 73, l964-l968 (l976).